crossing96/oncoscreening huggingface dataset:
Dose-Dependent Response to 3-Nitrobenzanthrone Exposure in Human Urothelial Cancer Cells.	A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterize the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 μM (environmentally relevant) to 80 μM by utilizing toxicological and metabolomic approaches. We observed that the RT4 cells were capable of bioactivation of 3-NBA within 30 min of exposure. Activity measurements of various enzymes involved in the conversion of 3-NBA in RT4 cells demonstrated NAD(P)H:quinone oxidoreductase (NQO1) as the main contributor for its bioactivation. Moreover, cytotoxicity assessment exhibited an initiation of adaptive mechanisms at low dosages, which diminished at higher doses, indicating that the capacity of these mechanisms no longer suffices, resulting in increased levels of intracellular reactive oxygen species, reduced proliferation, and hyperpolarisation of the mitochondrial membrane. To characterize the underlying mechanisms of this cellular response, the metabolism of 3-NBA and metabolomic changes in the cells were analyzed. The metabolomic analysis of the cells (0.0003, 0.01, 0.08, 10, and 80 μM 3-NBA) showed elevated levels of various antioxidants at low concentrations of 3-NBA. However, at higher exposure concentrations, it appeared that the cells reprogrammed their metabolism to maintain the cell homeostasis via activation of pentose phosphate pathway (PPP).	bladder
Can urologists accurately stage and grade urothelial bladder cancer by assessing endoscopic photographs?	Introduction Assessment of urothelial bladder cancer during cystoscopy or transurethral resection of bladder tumour has a significant impact on the urologist's decision-making: treatment with simple outpatient fulguration, required depth of resection, and need of immediate post-surgical intravesical therapy. These choices depend heavily on the urologist's ability to accurately assess pre-biopsy tumour stage and grade. The aim of the study was to determine whether evaluation of photographs taken during transurethral resection of bladder tumour can reliably characterize a tumour's stage and grade. Methods Smartphone photographs of 50 urothelial bladder cancer cases were taken at the beginning of transurethral resection of bladder tumour and individually presented to seven senior urologists. All urologists were blinded to the final pathological report and to any other urological evaluation. Each one was asked to rate the tumour as low vs high grade and noninvasive Ta vs noninvasive T1 or muscle invasive. Results were compared with final pathology. Individual appraisal and the majority's opinion were evaluated. Results Urologists have correctly predicted tumour stage and grade in 63.5% of cases (222 of 350, average of 32 out of 50 accurate assessments). The final majority assessment was correct in 40 of 50 cases (80%). Sensitivity and specificity of the final results for the diagnosis of T1 or higher were 80% and 88.6%, respectively. Sensitivity and specificity for Ta low grade were 83.3% and 80%, respectively. Conclusions To the best of our knowledge, this is the first documented attempt to evaluate urologists' ability to assess urothelial bladder cancer stage and grade using endoscopic photographs. Urologists can usually identify stage and grade of urothelial bladder cancer but accuracy increases when multiple senior urologists examine the same photographs and achieve majority consensus. Presenting photographs of urothelial bladder cancer to a team of urologists may lead to an excellent decision regarding type and extent of surgical treatment and substantiate appropriate post-surgical management.	bladder
Treatment Patterns and Survival Outcomes for Patients with Small Cell Carcinoma of the Bladder.	BACKGROUND: Small cell carcinoma of the bladder (SCCaB) is a rare tumor without a standard treatment algorithm. Treatment patterns and survival outcomes from the National Cancer Database (NCDB) may provide insight into optimal treatment strategies. OBJECTIVE: To investigate the relationship between overall survival (OS) and treatment strategy. DESIGN, SETTING, AND PARTICIPANTS: This was an observational study of treatment-naïve patients who received treatment from 2004 to 2013. Patients with cT1-4aN0M0 SCCaB were identified from the NCDB, a hospital-based tumor registry that captures >70% of incident cancer cases in the USA. INTERVENTION: Treatment strategies included local therapy alone, chemotherapy (CT), radiation therapy (RT), chemoradiation therapy (CRT), radical cystectomy (RC), and RC plus chemotherapy (RC+C). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS was analyzed as a function of treatment modality adjusting for patient, demographic, and tumor-related factors. The Kaplan-Meier survival method, and the log-rank test and Cox regression were used for univariable and multivariable analyses. RESULTS AND LIMITATIONS: We identified 856 patients with median follow-up of 18.3 mo. The median OS for the entire cohort was 20.7 mo (95% confidence interval [CI] 18.3-23.2) and estimated 3-yr and 5-yr OS were 37.5% and 28.2%, respectively. The most common treatment modality was CT (225 patients; 26.3%) followed by CRT (203 patients; 23.7%) and RC+C (201 patients; 23.5%). The median OS was 18.4 mo (95% CI 15.2-21.5) for CT, 34.1 mo (95% CI 22.5-45.8) for CRT, and 32.4 mo (95% CI 20.8-44.1) for RC+C. OS did not significantly differ between CRT and RC+C (p=0.42). On multivariable analysis, the best OS was associated with CRT (hazard ratio [HR] 0.41, 95% CI 0.32-0.53; p<0.0001) and RC+C (HR 0.45, 95% CI 0.34-0.59; p<0.0001). CONCLUSIONS: RC+C and CRT are associated with better OS compared to monotherapy among patients with SCCaB. PATIENT SUMMARY: Small cell carcinoma of the bladder is a rare and highly aggressive cancer. According to National Cancer Database data, radical cystectomy plus chemotherapy and chemoradiation therapy are associated with better overall survival compared to monotherapy.	bladder
Response Rate to Chemotherapy After Immune Checkpoint Inhibition in Metastatic Urothelial Cancer.	Immune checkpoint inhibitors (ICIs) are active in metastatic urothelial carcinoma (MUC). They have joined chemotherapy (CT) as a standard of care. Here, we investigate the activity of CT after progression on ICIs. Two cohorts of sequential patients with MUC were described (n=28). Cohort A received first-line ICIs followed by CT after progression. Cohort B received CT after failure of first-line platinum-based CT followed by ICIs. Response rate (RR) to CT was assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) by a designated radiologist. Best RR for cohort A was 64%. Two patients experienced clinical progression and died before the first radiographic assessment. RR for cohort B was 21%, which was significantly lower than that for cohort A. Progression of disease occurred in 43% of cohort B patients by the end of CT. These data suggest a lack of cross resistance between CT and ICIs in MUC. Therefore, the sequencing of these drugs is likely to be important to maximise outcomes. This is particularly true after first-line ICIs as subsequent CT has significant activity. PATIENT SUMMARY: In this report, we studied the effect of chemotherapy in metastatic bladder cancer, which relapsed after immune checkpoint inhibitors. We found that the activity of chemotherapy was maintained despite previous exposure to immune therapy. This underlines the importance of sequencing these agents to maximise outcomes.	bladder
Development of a Natural Language Processing Engine to Generate Bladder Cancer Pathology Data for Health Services Research.	OBJECTIVE: To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) engine that abstracts pathology data from full-text pathology reports. METHODS: Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer. RESULTS: When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer. CONCLUSION: NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data.	bladder
Current Trends in Cancer Biomarker Discovery Using Urinary Metabolomics: Achievements and New Challenges.	BACKGROUND: The development of effective screening methods for early cancer detection is one of the foremost challenges facing modern cancer research. Urinary metabolomics has recently emerged as a potentially transformative approach to cancer biomarker discovery owing to its noninvasive sampling characteristics and robust analytical feasibility. OBJECTIVE: To provide an overview of new developments in urinary metabolomics, cover the most promising aspects of hyphenated techniques in untargeted and targeted metabolomics, and to discuss technical and clinical limitations in addition to the emerging challenges in the field of urinary metabolomics and its application to cancer biomarker discovery. METHODS: A systematic review of research conducted in the past five years on the application of urinary metabolomics to cancer biomarker discovery was performed. Given the breadth of this topic, our review focused on the five most widely studied cancers employing urinary metabolomics approaches, including lung, breast, bladder, prostate, and ovarian cancers. RESULTS: As an extension of conventional metabolomics, urinary metabolomics has benefitted from recent technological developments in nuclear magnetic resonance, mass spectrometry, gas and liquid chromatography, and capillary electrophoresis that have improved urine metabolome coverage and analytical reproducibility. Extensive metabolic profiling in urine has revealed a significant number of altered metabolic pathways and putative biomarkers, including pteridines, modified nucleosides, and acylcarnitines, that have been associated with cancer development and progression. CONCLUSION: Urinary metabolomics presents a transformative new approach toward cancer biomarker discovery with high translational capacity to early cancer screening.	bladder
Smoking cessation and survival in lung, upper aero-digestive tract and bladder cancer: cohort study.	BACKGROUND: The aim was to examine the association between smoking cessation and prognosis in smoking-related cancer as it is unclear that cessation reduces mortality. METHODS: In this retrospective cohort study from 1999 to 2013, we assessed the association between cessation during the first year after diagnosis and all-cause and cancer-specific mortality. RESULTS: Of 2882 lung, 757 upper aero-digestive tract (UAT) and 1733 bladder cancer patients 27%, 29% and 21% of lung, UAT and bladder cancer patients quit smoking. In lung cancer patients that quit, all-cause mortality was significantly lower (HR: 0.82 (0.74-0.92), while cancer-specific mortality (HR: 0.89 (0.76-1.04) and death due to index cancer (HR: 0.90 (0.77-1.05) were non-significantly lower. In UAT cancer, all-cause mortality (HR: 0.81 (0.58-1.14), cancer-specific mortality (HR: 0.84 (0.48-1.45), and death due to index cancer (HR: 0.75 (0.42-1.34) were non-significantly lower. There was no evidence of an association between quitting and mortality in bladder cancer. The HRs were 1.02 (0.81-1.30) for all-cause, 1.23 (0.81-1.86) for cancer specific, and 1.25 (0.71-2.20) for death due to index cancer. These showed a non-significantly lower risk in sensitivity analyses. CONCLUSIONS: People with lung and possibly UAT cancer who quit smoking have a lower risk of mortality than people who continue smoking.	bladder
Long-term kidney transplant survival in patients with continent urinary diversion.	OBJECTIVES: To report the long-term survival of transplanted kidneys in patients with a continent urinary diversion. METHODS: Between January 1987 and July 2015, 16 patients with a median age of 37 years (range 21-63 years) underwent kidney transplantation on a continent urinary diversion. A total of 14 patients presented irreversible dysfunction of the lower urinary tract, and two patients had required radical cystectomy because of bladder cancer. All continent urinary diversions were carried out before the transplantation. There were nine Kock pouches, five Mainz pouches, one Mainz neobladder and one Hautmann neobladder. A total of 11 patients had a previous non-continent urinary diversion. Of the transplants, 14 came from brain-dead donors and two from related living donors. RESULTS: The median post-transplantation follow up was 171 months (range 30-298 months). Two patients died, while six patients lost their transplant and resumed hemodialysis. Nine patients (56.2%) were alive with a functional transplant at the end of follow up. The most common allograft complication was acute pyelonephritis, but no graft was lost as a result of urinary diversion complications. The kidney transplant survival rate was 73.3% after 10 years, and 66.6% after 15 years. Among patients who still had a functional transplant at the time of the study, creatinine clearance was >30 mL/min for seven patients and <30 mL/min for two patients. CONCLUSIONS: The present study is the longest series to date of renal transplantation on continent urinary diversions. The long-term outcome shows that the presence of a continent urinary diversion does not reduce transplant survival.	bladder
Detection of APOBEC3 Proteins and Catalytic Activity in Urothelial Carcinoma.	Members of the APOBEC3 (A3) family of enzymes were shown to act in an oncogenic manner in several cancer types. Immunodetection of APOBEC3A (A3A), APOBEC3B (A3B), and APOBEC3G (A3G) proteins is particularly challenging due to the large sequence homology of these proteins and limited availability of antibodies. Here we combine independent immunoblotting with an in vitro activity assay technique, to detect and categorize specific A3s expressed in urothelial bladder cancer and other cancer cells.	bladder
Gender-specific Differences in Recurrence of Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.	CONTEXT: The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB. OBJECTIVE: To conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC). EVIDENCE ACQUISITION: An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggeŕs test. EVIDENCE SYNTHESIS: Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence. CONCLUSIONS: Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses. PATIENT SUMMARY: In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men.	bladder
Predicting local failure after radical cystectomy in patients with bladder cancer: Implications for the selection of candidates at adjuvant radiation therapy.	OBJECTIVE: To evaluate incidence and predictors of local failure (LF) after radical cystectomy (RC) due to bladder cancer. METHODS: We focused on 1,112 patients treated with RC, between 1990 and 2012, at a single center. LF was defined as imaging evidence of recurrence in the pelvic soft tissues or nodes below the aortic bifurcation at least 3 months before the detection of distant metastases. Competing risk analyses tested the relationship between clinical and pathological factors and the risk to develop LF. Regression tree analysis stratified patients into risk-groups based on their characteristics and the corresponding LF rate. RESULTS: Overall, 50 (4.5%) patients developed LF during a median follow-up period of 62 (35-92) months. On univariable competing risk regression analyses, pathological T stage (pT4 vs. pT3; hazard ratio [HR] = 2.55, P = 0.003), soft tissue surgical margin (STSM; HR = 2.95, P = 0.005), and variant histology (HR = 1.79, P = 0.03) were associated with an increased risk of developing LF. The cohort was stratified into 4 risk groups: very low (≤pT3a disease and pure urothelial histology), low (≤pT3a disease and variant histology), intermediate (pT4 disease), and high (positive STSM). CONCLUSIONS: LF is an important event in RC patients. We developed a new risk model based on bladder cancer characteristics. Our findings could help with the identification of the best candidate for consideration of adjuvant radiotherapy.	bladder
An Inexpensive, Point-of-Care Urine Test for Bladder Cancer in Patients Undergoing Hematuria Evaluation.	"Although hematuria (blood in urine) is the most common symptom of bladder cancer, 70-98% of hematuria cases are benign. These hematuria patients unnecessarily undergo costly, invasive, and expensive evaluation for bladder cancer. Therefore, there remains a need for noninvasive office-based tests that can rapidly and reliably rule out bladder cancer in patients undergoing hematuria evaluation. Herein, a clinical assay for matrix metalloproteinases (""Ammps"") is presented, which generates a visual signal based on the collagenase activity (in urine of patients) on the Ammps substrates. Ammps substrates are generated by crosslinking gelatin with Fe(II) chelated alginate nanoparticles, which precipitate in urine samples. The cleavage of gelatin-conjugated alginate (Fe(II)) nanoparticles by collagenases generates free-floating alginate (Fe(II)) nanoparticles that participate in Fenton's reaction to generate a visual signal. In a pilot study of 88 patients, Ammps had 100% sensitivity, 85% specificity, and a negative predictive value (NPV) of 100% for diagnosing bladder cancer. This high NPV can be useful in ruling out bladder cancer in patients referred for hematuria evaluation."	bladder
The Cancer of the Bladder Risk Assessment (COBRA) score: Estimating mortality after radical cystectomy.	BACKGROUND: Risk stratification of patients with urothelial carcinoma of the bladder (UCB) after cystectomy has important clinical and research implications. The authors assessed the relative effect of tumor stage and lymph node status on cancer-specific survival (CSS) after cystectomy and developed a simplified risk-assessment tool. METHODS: In total, 14,828 patients who underwent cystectomy with lymph node dissection for UCB were identified from the Surveillance, Epidemiology, and End Results database (1988-2011). The relative importance of tumor stage and lymph node status with regard to CSS was assessed using stratified Kaplan-Meier and Cox proportional-hazards analyses. The patients were split randomly into development and validation cohorts. Additional validation using overall survival was performed on 19,362 patients from the National Cancer Data Base. The Cancer of Bladder Risk Assessment (COBRA) tool was created using a Cox model incorporating age, tumor stage, and lymph node density. Performance was validated using observed versus expected survival plots and the Harrell concordance index. RESULTS: Patients with muscle invasive (T2), lymph node-positive disease had a survival curve similar to that in patients with extravesical (T3 and T4), lymph node-negative disease (2-year CSS, 67% and 70%, respectively). Each point increase in the COBRA score (range, 0-7) was associated with a 1.61-fold increase (95% confidence interval, 1.56-fold to 1.65-fold increase) in the risk of bladder cancer death in the development cohort. The model accurately stratified patients across risk levels in the development cohort and the 2 validation cohorts (C-index, 0.712, 0.705, and 0.68, respectively). CONCLUSIONS: The COBRA score offers a straightforward, validated risk-stratification tool that incorporates the relative contribution of tumor stage and lymph node involvement to patient prognosis after cystectomy for UCB. Cancer 2017;123:4574-4582. © 2017 American Cancer Society.	bladder